Abstract The aim of this proposal is to acquire a new Bruker Skyscan 1176 high-resolution, in vivo microcomputed tomography (microCT) X-Ray imaging system. Three-dimensional imaging via microCT has become a standard technique for non-destructive, quantitative analysis of mineralized tissue structure, and recent advances in contrast and non-contrast-based approaches have allowed quantitative, 3D analysis of microvasculature and soft-tissue structure and composition. Existing in vivo microCT systems at Stanford are aging and offer a best resolution of approximately 50m, and thus are not adequate for many modern research requirements. Additionally, many projects require higher resolution scanning for detailed, post-mortem morphological analysis of bony structures or analysis of specimen composition and structure. The Bruker SkyScan 1176 offers a unique combination of capabilities addressing a wide range of in vivo and specimen scanning needs. In vivo scans at 70m voxel size resolution can be performed in less than a minute with only 9mGy radiation dose, compared to the ~90mGy dose delivered by our existing RS150 scanner at 96m voxel size. The 68mm bore diameter and 200mm scannable length allow whole body scanning of live animals up to the size of rats and small rabbits, as well as limbs of other animals. For specimen scanning, high resolution scans can be performed at resolutions as fine as 9m. The SkyScan 1176 will be installed in the Stanford Center for Innovation in In Vivo Imaging (SCI3) Small Animal Imaging Facility, a centrally located core facility open and accessible to researchers from across Stanford. The SCI3 is a world-class facility for imaging of small animal models of disease, providing equipment for a wide range of imaging modalities and a well-established, successful infrastructure for user training, instrument scheduling and system maintenance. Stanford University will further support the establishment of this new core resource by committing to $15,000 per year for two years to help cover the instrument service contract costs. The SkyScan 1176 will initially support at least seven R01, one R21, and one P01 funded NIH grants in addition to unfunded projects laying the foundation for future NIH proposals. Faculty from nine departments in the Schools of Medicine and Engineering will initially exploit this state-of-the-art instrument to pursue research relevant to multiple human diseases, including study of cancer biology, bone and soft tissue biomechanics and pathologies, tissue engineering and stem cell therapies. The investigators comprising the microCT user group have an established record of translation of basic and preclinical research into clinical practice, ensuring the research performed using this device will be rigorously focused on the treatment of human disease.